title: Synergistic inhibition of natural killer cells by the nonsignaling molecule CD94.
abstract: Peptide selectivity is a feature of inhibitory receptors for MHC class I expressed by natural killer (NK) cells. CD94-NKG2A operates in tandem with the polymorphic killer cell Ig-like receptors (KIR) and Ly49 systems to inhibit NK cells. However, the benefits of having two distinct inhibitory receptor-ligand systems are not clear. We show that noninhibitory peptides presented by HLA-E can augment the inhibition of NKG2A(+) NK cells mediated by MHC class I signal peptides through the engagement of CD94 without a signaling partner. Thus, CD94 is a peptide-selective NK cell receptor, and NK cells can be regulated by nonsignaling interactions. We also show that KIR(+) and NKG2A(+) NK cells respond with differing stoichiometries to MHC class I down-regulation. MHC-I-bound peptide functions as a molecular rheostat controlling NK cell function. Selected peptides which in isolation do not inhibit NK cells can have different effects on KIR and NKG2A receptors. Thus, these two inhibitory systems may complement each other by having distinct responses to bound peptide and surface levels of MHC class I.
authors.affiliation: Division of Medicine , Imperial College London, London W2 1PG, United Kingdom.
authors.forename: Kuldeep S
authors.initials: KS
authors.lastname: Cheent
authors.forename: Khaleel M
authors.initials: KM
authors.lastname: Jamil
authors.forename: Sorcha
authors.initials: S
authors.lastname: Cassidy
authors.forename: Mengya
authors.initials: M
authors.lastname: Liu
authors.forename: Berenice
authors.initials: B
authors.lastname: Mbiribindi
authors.forename: Arend
authors.initials: A
authors.lastname: Mulder
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Marco A
authors.initials: MA
authors.lastname: Purbhoo
authors.forename: Salim I
authors.initials: SI
authors.lastname: Khakoo
mesh_terms: D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology*; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology / Q000378:metabolism; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D054340:Receptors, KIR / Q000276:immunology / Q000378:metabolism; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides; D054340:Receptors, KIR; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human
keywords: MHC-I peptides; innate immunity